Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta.
Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta.
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发表时间：
1991-09
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通讯作者：
N. Jaiswal;G. Lambrecht;E. Mutschler;R. Tacke;K. Malik
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作者：
N. Jaiswal;G. Lambrecht;E. Mutschler;R. Tacke;K. Malik
在去甲肾上腺素预收缩的兔主动脉环中进行了研究，以确定胆碱能刺激引起内皮依赖性松弛和收缩的胆碱碱受体亚型。乙酰胆碱（ACh）和槟碱丙炔酯（APE）是一种M2和M3激动剂，分别在内皮完好和剥离的兔主动脉环中产生剂量依赖性的舒张和收缩。这两种反应都被毒蕈碱受体拮抗剂阿托品阻断。M1选择性激动剂McN-A-343 [4-[N-（3-氯苯基）氨基氧基]-2-丁基三甲基铵++ +氯化物]对预收缩主动脉环的张力没有任何影响。M3受体拮抗剂六氢硅氧烷二苯醚和对氟六氢硅氧烷二苯醚（pA2分别为7.84和7.18）可选择性阻断ACh-和ape诱导的内皮完整的主动脉环松弛，而M1受体拮抗剂吡仑平或M2受体拮抗剂AF-DX 116[11-(2-[（二乙胺）甲基]- 1-哌替啶基]乙酰基]- 5,11 -二氢- 6h -吡啶-[2,3-b][1,4]-苯并二氮平-6-酮]和甲氧曲明不能阻断ACh-和ape诱导的内皮完整的主动脉环松弛。M2受体拮抗剂AF-DX 116和甲氧曲明（pA2分别为7.11和6.71）对ACh-和ape诱导的收缩有抑制作用，而吡仑西平、六氢硅氧烷二苯醚和对氟六氢硅氧烷二苯醚无抑制作用。烟碱受体拮抗剂六甲氧铵或环氧化酶抑制剂吲哚美辛不改变乙酰胆碱和乙酰胆碱诱导的松弛或收缩。这些数据表明，胆碱能刺激素在内皮完好的主动脉环中引起的松弛是通过内皮细胞上的M3受体激活后内皮源性松弛因子的释放介导的，而在剥离内皮的主动脉环中，收缩是通过平滑肌细胞上的M2受体的刺激介导的。
Studies were performed in the rabbit aortic rings, precontracted with norepinephrine, to determine the subtype(s) of muscarinic receptors involved in endothelium-dependent relaxation and contraction in the absence of endothelium elicited by cholinergic stimuli. Acetylcholine (ACh) and arecaidine propargyl ester (APE), a M2 and M3 agonist, produced a dose-dependent relaxation and contraction in endothelium-intact and endothelium-denuded rabbit aortic rings, respectively. Both of these responses were blocked by the muscarinic receptor antagonist atropine. M1 selective agonist McN-A-343 [4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium+ ++ chloride] did not produce any effect on the tone of precontracted aortic rings. ACh- and APE-induced relaxation in aortic rings with intact endothelium was selectively blocked by M3 receptor antagonists hexahydrosila-difenidol and p-fluoro-hexahydro-sila-difenidol (pA2 of 7.84 and 7.18) but not by M1 antagonist pirenzepine or M2 receptor antagonists AF-DX 116 [11-(2-[(diethylamino)methyl]- 1-piperidinyl]acetyl)-5, 11-dihydro-6H-pyrido-[2,3-b][1,4]-benzo-diazepin-6-one] and methoctramine. ACh- and APE-induced contraction was inhibited by M2 receptor antagonists AF-DX 116 and methoctramine (pA2 of 7.11 and 6.71) but not by pirenzepine, hexahydro-sila-difenidol or p-fluoro-hexahydro-sila-difenidol. ACh- and APE-induced relaxation or contraction were not altered by nicotinic receptor antagonist hexamethonium or cyclooxygenase inhibitor indomethacin. These data suggest that relaxation elicited by cholinergic stimulin in endothelium-intact aortic rings is mediated via release of endothelium-derived relaxing factor consequent to activation of M3 receptors located on endothelial cells, whereas the contraction in aortic rings denuded of their endothelium is mediated via stimulation of M2 receptors located on smooth muscle cells.